ALK (anaplastic lymphoma kinase) activation in cancer was discovered in anaplastic large-cell non-Hodgkin’s lymphoma, followed by non-small cell lung cancer. Since then, several human cancers have reported to present ALK alterations, such as translocation, overexpression and mutation. ALK-tyrosine kinase inhibitors are reported to be effective in some of these cancers.
TACKLE (NCCH1712/MK003) is a phase II study designed to evaluate efficacy and safety of alectinib in patients with ALK-positive advanced rare cancer. This study is conducted as part of the MASTER KEY project, which is a basket/umbrella trial including a registry study for rare cancers (UMIN000027552). ALK-positive was defined as follow, 1) translocation, 2) activating mutation, 3) overexpression. Rare cancer was defined as "annual incidence < 6 / 100,000 population". Patients who have unresectable disease, age ≥ 16, PS of 0-1 and completed standard treatment were eligible. All patients are screened for ALK alterations by genomic profiling assays based on next-generation sequencing technology mainly by FoundationOne®. Patients will receive alectinib 300 mg bid until disease progression, unacceptable toxicity, treatment discontinuation at the discrestion of the investigator or patient, or death. Primary endpoint is response rate (central assessment), and secondary endpoints include progression free survival, overall survival, stable disease rate and toxicity. Approximately 15 to 20 patients will be enrolled depending on Bayesian sample-size determination and adaptive design. Enrollment is ongoing. Participating sites are National Cancer Center and Kyoto University Hospital, and will be expanding shortly.